Director, Drug Product SME

Job description

Madrigal is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a serious liver disease that can progress to cirrhosis, liver failure, need for liver transplantation and premature mortality. Every member of our Madrigal team is connected by our shared purpose: leading the fight against MASH. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. Rezdiffra is the first and only medication approved by both the FDA and European Commission for the treatment of MASH with moderate to advanced fibrosis (F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (F4c). Our success is driven by our people. We are building a dynamic, inclusive, and high-performing culture that values scientific excellence, operational rigor, and collaboration. To support our continued growth, we are strengthening our workforce strategy to ensure we have the right talent, at the right time, in the right way. The Director, Drug Product SME is an experienced scientific leader, with responsibility for advancing the CMC development of Madrigal’s siRNA/oligonucleotide and small molecule portfolio. This role focuses on drug product formulation and process development, ensuring preclinical and clinical studies are supported with phase appropriate quality investigational medicinal product, delivered on time and guided by scientific rigor, risk assessment and data-driven decision-making. As a key member of CMC development project teams within Technical Operations, this leader will also serve as a program-level CMC lead across preclinical development, clinical development, scale-up, registration, and commercialization. The Director is expected to lead at least one cross-functional CMC team supporting the development of a clinical-stage asset. This role executes drug product development deliverables by translating drug product strategy into protocols, data packages, and external partner deliverables. Responsibilities include leading hands-on technical evaluation of formulation and processing options, supporting drug product troubleshooting; ensuring readiness and oversight for clinical supply manufacture. The Director will produce high-quality reports and documentation inputs that support CMC authoring, regulatory traceability, and program decision-making. This role requires strong internal partnership with Quality, Research, Regulatory Affairs, Drug Safety, Clinical, and Supply Chain teams, as well as effective oversight of external CDMO and CRO relationships supporting candidate development across all phases. Ultimately, the ideal candidate is a collaborative technical leader, with expertise in siRNA/oligonucleotide modalities, who can build and contribute to a high-performing Pharmaceutical Science team supporting the development of an industry-leading NASH/MASH-focused pipeline. Key Responsibilities: Drug Product Development and Technical Strategy Lead or support generation of comprehensive pre-formulation data packages and asset profiles to inform developability assessment, development strategy, and program planning. Lead or support phase-appropriate development, optimization, and delivery of siRNA/oligonucleotide and small-molecule formulations, associated processes, and material supply from preclinical through early clinical development. For small-molecule candidates, lead or support formulation and process strategies to address bioavailability risks and enable fixed-dose combination development with Rezdiffra® (resmetirom), where applicable. Lead or support registration, final scale-up, process validation, and commercial presentation development in accordance with cGMP, ICH, FDA, and internal target product profile requirements. External Partner and CDMO Oversight Serve as the primary drug product contact for CDMOs and oversee key deliverables, including protocols, batch records, reports, investigations, and technical documentation. Troubleshoot drug product issues, develop root-cause hypotheses, and coordinate resolution with cross-functional internal and external partners. Support drug product technology transfer readiness, including process descriptions, control strategies, sampling plans, comparability considerations, and transfer documentation. Support leadership and Global Procurement in defining and maintaining a CDMO/CRO network that meets current and future CMC business, regulatory, and quality needs. Quality, Regulatory, and CMC Documentation Implement Quality-by-Design and Quality Risk Management principles throughout the development lifecycle, ensuring clear decision logs, assumptions, data traceability, and alignment with Quality, Regulatory, and Supply Chain standards. Ensure adherence to sound decision-making processes established through strong scientific rigor and robust data, leveraging cross-functional expertise. Use statistical design-of-experiment practices and AI-enabled tools, to increase efficiency and effectiveness in generating CMC knowledge and phase-appropriate control strategies. Author, compile, and review drug product technical reports, regulatory source data, CMC regulatory documents, and quality documentation as required. Provide direction and oversight for authoring and reviewing Module 3 eCTD content for INDs, NDAs, meeting briefing books, and other regulatory submissions. Review quality agreements, participate in audit programs, maintain inspection readiness, and represent the company as a CMC subject matter expert in regulatory inspections and audits as required. Cross-Functional Leadership and Operational Excellence Partner across Technical Operations, MSAT, Quality, Research, Regulatory Affairs, Drug Safety, Clinical, Supply Chain, and other stakeholders to ensure alignment across all stages of development. Promote early development collaboration with MSAT to support future product robustness, supply resilience, and cost efficiency. Support creation, submission, and tracking of fiscally responsible project budgets aligned with phase-appropriate and risk-tolerant project goals. Champion a Right First-Time culture focused on data integrity, scientific rigor, continuous improvement, and operational excellence across CMC and Technical Operations. Qualifications and Skills Required: Education: PhD degree in Pharmaceutics, Chemistry or Material Sciences, or BS/MS degree and commensurate Pharmaceutical Science development and leadership experience. Experience: Minimum of 15 years of experience in Pharmaceutical Science and CMC leadership within the biopharmaceutical industry, with a strong background in CMC and Drug Product development. Proven experience in siRNA/oligonucleotide drug product formulation/process development is a must. Experience in small molecule drug product formulation/process development is desirable. Proven experience in working with CDMO/CRO’s in a fully outsourced paradigm, providing technical leadership and oversight to development & clinical supply manufacture, and driving technical solutions in an external environment. On-boarding and accelerating the mobilizing of new assets post-acquisition is desirable. Demonstrated success in transitioning programs from clinical development to commercial manufacturing, including process validation and regulatory approval, in a cross-functional matrixed organization. Working knowledge of statistical design of experimental approaches, execution and analysis, development of CMC risk assessments & control strategies. Strong knowledge of cGMP and ICH guidelines, global regulatory requirements and regulatory document authoring. Regulatory agency interactions is desirable. Skills: Strategic and operational leader with a balance of scientific depth and business acumen. Strong Leadership skills with an ability to both influence and empower. Strong technical ex